Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distributi...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
The Company of Biologists
2021
|
| _version_ | 1826285339971420160 |
|---|---|
| author | Cahill, TJ Sun, X Ravaud, C Villa Del Campo, C Klaourakis, K Lupu, I-E Lord, AM Brown, C Jacobsen, S Greaves, D Jackson, D Cowley, S James, W Choudhury, RP Vieira, J Riley, P |
| author_facet | Cahill, TJ Sun, X Ravaud, C Villa Del Campo, C Klaourakis, K Lupu, I-E Lord, AM Brown, C Jacobsen, S Greaves, D Jackson, D Cowley, S James, W Choudhury, RP Vieira, J Riley, P |
| author_sort | Cahill, TJ |
| collection | OXFORD |
| description | Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1+ myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature. |
| first_indexed | 2024-03-07T01:27:22Z |
| format | Journal article |
| id | oxford-uuid:926c23f1-f578-43dd-9e24-8693e3d072fe |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:27:22Z |
| publishDate | 2021 |
| publisher | The Company of Biologists |
| record_format | dspace |
| spelling | oxford-uuid:926c23f1-f578-43dd-9e24-8693e3d072fe2022-03-26T23:25:29ZTissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heartJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:926c23f1-f578-43dd-9e24-8693e3d072feEnglishSymplectic ElementsThe Company of Biologists2021Cahill, TJSun, XRavaud, CVilla Del Campo, CKlaourakis, KLupu, I-ELord, AMBrown, CJacobsen, SGreaves, DJackson, DCowley, SJames, WChoudhury, RPVieira, JRiley, PMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1+ myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature. |
| spellingShingle | Cahill, TJ Sun, X Ravaud, C Villa Del Campo, C Klaourakis, K Lupu, I-E Lord, AM Brown, C Jacobsen, S Greaves, D Jackson, D Cowley, S James, W Choudhury, RP Vieira, J Riley, P Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title | Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title_full | Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title_fullStr | Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title_full_unstemmed | Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title_short | Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| title_sort | tissue resident macrophages regulate lymphatic vessel growth and patterning in the developing heart |
| work_keys_str_mv | AT cahilltj tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT sunx tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT ravaudc tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT villadelcampoc tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT klaourakisk tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT lupuie tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT lordam tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT brownc tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT jacobsens tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT greavesd tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT jacksond tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT cowleys tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT jamesw tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT choudhuryrp tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT vieiraj tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart AT rileyp tissueresidentmacrophagesregulatelymphaticvesselgrowthandpatterninginthedevelopingheart |